Objective: To investigate the value of drain fluid amylase level obtained on the first postoperative day (DFA1) in predicting pancreatic fistula (PF). Methods: The clinical data of all patients undergoing pancreatic resection from February 2011 to February 2016 in the Affiliated Hospital of Taishan Medical College and FeichengKuangye Central Hospital were reviewed, and those with DFA1 data were selected. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of DFA1 for predicting PF were analyzed by receiver operating characteristic (ROC) curve, and the risk factors for PF were also determined. Results: A total of 125 patients underwent pancreatic resection and 67 cases (55 cases undergoing pancreaticoduodenectomy and 12 cases undergoing distal pancreatectomy) of them had DFA1 data. Of the 67 patients, PF occurred in 15 cases, which was classified as grade A in 7 cases (10.45%), grade B in 6 cases (8.96%) as and grade C in 2 cases (2.99%). ROC curve analysis showed that DFA1 had significant predictability on PF (P<0.05), and the sensitivity, specificity, PPV and NPV were 100%, 80.8%, 60.0% and 100.0% respectively at the cutoff value of 340 U/L. Univariate analysis indicated that DFA1, pancreatic duct diameter ≤ 3 mm and soft pancreatic texture were risk factors for PF (all P<0.05), and the Logistic regression analysis identified that DFA1 was an independent risk factor for PF (P<0.05). Conclusion: DFA1 is an independent risk factor for PF and has better value in predicting PF. Aggressive preventive measures should be made against PF in patients with DFA1>340 U/L.